[Leish-l] Fwd: Articles found by RefScout 2006/03/29 2006/13
jeffreyj at usp.br
jeffreyj at usp.br
Mon Apr 10 07:43:33 BRT 2006
Date: Wed, 29 Mar 2006 04:16:18
From: info at refscout.com
New!
Have a look at our new tool, the RefScout‘s PDF-Manager (PDFM)! The RefScout‘s
PDFM will revolutionize your life with PDF files!
Simply let your PDF files be organized by the RefScout‘s PDFM in a table and get
direct link to your local copy. In addition, the RefScout‘s PDFM will alert you
each time the NLM PubMed updates information concerning your specific
reference!
Get your free 2 months trial version now at RefScout’s PDF-Manager.
This is RefScout-Newsletter 13/2006.
REQUEST: [ leishmaniasis ]
(8 articles match this request)
PMID: 16481076
TITLE: Comparison of potential protection induced by three vaccination
strategies (DNA/DNA, Protein/Protein and DNA/Protein) against Leishmania major
infection using Signal Peptidase type I in BALB/c mice.
AUTHORS: Sima Rafati, Fatemeh Ghaemimanesh, Farnaz Zahedifard
AFFILIATION: Molecular Immunology and Vaccine Research Lab., Pasteur Institute
of Iran, P.O. Box 11365-6699, Tehran, Iran.
REFERENCE: Vaccine 2006 Apr 24(16):3290-7
Signal Peptidase (SPase) is an essential enzyme in both prokaryotes and
eukaryotes; which removes signal sequence from secretary proteins.
Previously, type I SPase from Leishmania major (Lmjsp) has been isolated
and characterized. The sera from cutaneous and visceral forms of
leishmaniasis are highly reactive to both the recombinant SPase (rSP)
and synthetic SPase (Sy-Sp) antigens. Therefore, the Leishmania SPase,
albeit localized intracellularly, is a significant target of the
Leishmania specific immune response and highlights its use as a
candidate vaccine against cutaneous leishmaniasis (CL). In this study as
a first report, the potential protection of Lmjsp was evaluated in
three different vaccination strategies (DNA/DNA, Protein/Protein and DNA
/Protein), against L. major infection. We demonstrated that vaccination
with SPase through all three mentioned strategies induced a parasite
specific Th1 response and conferred partial protection against parasite
challenge. However, our results indicated that DNA/DNA strategy
developed more effective protective responses than the other two
approaches and induced 81% reduction in L. major parasite load.
PMID: 16556218
TITLE: A novel high-affinity arginine transporter from the human parasitic
protozoan Leishmania donovani.
AUTHORS: Pninit Shaked-Mishan, Marianne Suter-Grotemeyer, Tamar Yoel-Almagor,
Neta Holland, Dan Zilberstein, Doris Rentsch
AFFILIATION: Department of Biology, Technion-Israel Institute of Technology,
Haifa 32000, Israel.
REFERENCE: Mol Microbiol 2006 Apr 60(1):30-8
We describe the first functional and molecular characterization of an
amino acid permease (LdAAP3) from the human parasitic protozoan
Leishmania donovani, the causative agent of visceral leishmaniasis in
humans. This permease contains 480 amino acids with 11 predicted trans-
membrane domains. Expressing LdAAP3 in Saccharomyces cerevisiae mutants
revealed that LdAAP3 codes for a high-affinity arginine transporter (K(m
) 1.9 microM). LdAAP3 is highly specific for arginine as its transport
was not inhibited by other amino acids or arginine-related compounds.
Using green fluorescence protein (GFP) fused to the N-terminus of LdAAP3
, this transporter was localized to the surface membrane of
promastigotes. The GFP-LdAAP3 chimera mediated a threefold increase in
arginine transport in promastigotes, indicating that it is active and
confirmed that LdAAP3 codes for an arginine transporter in parasite
cells as well. LdAAP3 is novel as it shares a high level of homology
with amino acid permeases from other trypanosomatidae but almost none
with permeases from other phyla. The results of this work suggest that
LdAAP3 might play a role in host-parasite interaction.
PMID: 16418337
TITLE: Antimony-based antileishmanial compounds prolong the cardiac action
potential by an increase in cardiac calcium currents.
AUTHORS: Yuri A Kuryshev, Lu Wang, Barbara A Wible, Xiaoping Wan, Eckhard
Ficker
AFFILIATION: Rammelkamp Center, MetroHealth Medical Center, 2500 MetroHealth
Drive, Cleveland, OH 44109. eficker at metrohealth.org.
REFERENCE: Mol Pharmacol 2006 Apr 69(4):1216-25
Antimonial agents are a mainstay for the treatment of leishmaniasis, a
group of protozoal diseases that includes visceral leishmaniasis, or
Kala Azar. Chemotherapy with trivalent potassium antimony tartrate (PAT
) and, more importantly, pentavalent antimony-carbohydrate complexes,
such as sodium stibogluconate (SSG), has been reported to prolong the QT
interval and produce life-threatening arrhythmias. PAT is chemically
related to As(2)O(3), which alters cardiac excitability by inhibition of
human ether a-go-go related gene (hERG) trafficking and an increase of
cardiac calcium currents. In this study, we report that PAT does not
block hERG currents on short-term exposure but reduces current density
on long-term exposure (IC(50), 11.8 muM) and inhibits hERG maturation on
Western blots (IC(50), 62 muM). Therapeutic concentrations of 0.3 muM
PAT increase cardiac calcium currents from -4.8 +/- 0.7 to -7.3 +/- 0.5
pA/pF at 10 mV. In marked contrast, pentavalent SSG, the drug of choice
for the treatment of leishmaniasis, did not affect hERG/I(Kr) or any
other cardiac potassium current at therapeutic concentrations. However,
both cardiac sodium and calcium currents were significantly increased on
long-term exposure to 30 muM SSG in isolated guinea pig ventricular
myocytes. We propose that the increase in calcium currents from -3.2
+/- 0.3 to -5.1 +/- 0.3 pA/pF at 10 mV prolongs APD(90) from 464 +/- 35
to 892 +/- 64 ms. Our data suggest that conversion of Sb(V) into active
Sb(III) in patients produces a common mode of action for antimonial
drugs, which define a novel compound class that increases cardiac risk
not by a reduction of hERG/I(Kr) currents but-for the first time-by an
increase in cardiac calcium currents.
PMID: 16369915
TITLE: RNA interference reveals a role for TLR2 and TLR3 in the recognition of
Leishmania donovani promastigotes by interferon-gamma-primed macrophages.
AUTHORS: Jean-Frédéric Flandin, Frédéric Chano, Albert Descoteaux
AFFILIATION: INRS- Institut Armand-Frappier and Centre for host-parasite
interactions, Laval QC, Canada H7V 1B7.
REFERENCE: Eur J Immunol 2006 Feb 36(2):411-20
Leishmania donovani promastigotes evade the induction of a
proinflammatory response during their invasion of naive macrophages.
However, their entry into IFN-gamma-primed macrophages is accompanied by
the secretion of nitric oxide (NO) and proinflammatory cytokines. In
the present study, we addressed the hypothesis that priming with IFN-
gamma induces the expression of a receptor that enables mouse
macrophages to recognize L. donovani promastigotes. We observed that in
IFN-gamma-primed macrophages, L. donovani promastigotes stimulated
Interleukin-1 receptor-associated kinase-1 (IRAK-1) activity. We next
showed that Toll-like receptor (TLR)3 is barely detectable in naive
macrophages but is expressed in IFN-gamma-treated macrophages. Silencing
of TLR3, TLR2, IRAK-1 and myeloid differentiation factor 88 (MyD88)
expression by RNA interference revealed that both TLR are involved in
the secretion of NO and TNF-alpha induced by L. donovani promastigotes.
Using L. donovani mutants, we showed that TLR2-mediated responses are
dependent on Galbeta1,4Manalpha-PO(4)-containing phosphoglycans, whereas
TLR3-mediated responses are independent of these glycoconjugates.
Furthermore, our data indicate a participation of TLR2 and TLR3 in the
phagocytosis of L. donovani promastigotes and a role for TLR3 in the
leishmanicidal activity of the IFN-gamma-primed macrophages.
Collectively, our data are consistent with a model where recognition of
L. donovani promastigotes depends on the macrophage activation status
and requires the expression of TLR3.
PMID: 16555721
TITLE: [Immunofluorescence assay with Crithidia luciliae for the detection of
anti-DNA antibodies. Atypical images and their relationship with Chagas'
disease and leishmaniasis]
AUTHORS: Gloria Griemberg, Nidia F Ferrarotti, Graciela Svibel, Maria R Ravelli,
Nestor J Taranto, Emilio L Malchiodi, Maria C Pizzimenti
AFFILIATION: Laboratorio de InmunologÃa, Departamento de BioquÃmica ClÃnica,
Facultad de Farmacia y BioquÃmica, Hospital de ClÃnicas José de San MartÃn,
Universidad de Buenos Aires, Argentina. ggriemberg at sinectis.com.ar
REFERENCE: Medicina (B Aires) 2006 66(1):3-8
Anti-native DNA antibodies can be detected by indirect
immunofluorescence assay with Crithidia luciliae, displaying an annular
image due to a kinetoplast containing double stranded DNA. Other
structures such as membrane, flagellum and basal corpuscle can be
stained as well, showing what is called atypical fluorescent images. As
C. luciliae belongs to the Trypanosomatidae family, which include the
human pathogens Trypanosoma cruzi and Leishmania spp., it was considered
that these atypical images could be caused by cross-reactions.
Serological studies for Chagas' disease were performed in 105 serum
samples displaying atypical images. Sixty four percent of the samples
from non endemic and 78.3% from endemic areas for Chagas' disease showed
fluorescence in both, membrane and flagellum (joint image). Fifty
samples from normal blood donors and 57 samples from patients with
conective tissue diseases were tested with C. luciliae. None of them
presented the joint image except for two patients with lupus who were
also chagasic. In addition, 54 samples from chagasic patients were
studied and all of them presented the joint image. We also studied 46
samples from patients with leishmaniasis from whom 28 were coinfected
with T. cruzi. The joint image was observed in 88.0% of the samples with
leishmaniasis and in 89.3% of the co-infected samples. The results
suggest that C. luciliae could be used as an economical, and of low risk
, alternative substrate for the serological diagnosis of Chagas' disease
, even though it does not discriminate for Leishmania spp. infection.
This study also suggests that whenever atypical images are observed in C
. luciliae during the search for anti-DNA antibodies, it would be
convenient to submit the patient to clinical and serological tests for
the diagnosis of leishmaniosis and Chagas' disease.
PMID: 16555523
TITLE: [Three cases of visceral leishmaniasis in Abidjan, Cote d'Ivoire]
AUTHORS: B Kouassi, K Horo, V H Achi, K D Adoubryn, E S Kakou, B Ahui, E
Aka-Danguy, A S N'Gom, N Koffi, B Padja
AFFILIATION: Service de pneumologie, CHU de Cocody, Abidjan, Côte d'Ivoire.
bokokouassi at hotmail.com
REFERENCE: Med Trop (Mars) 2005 Nov 65(6):602-3
Three cases of visceral leishmaniasis were observed in a cohort of 528
patients admitted to the Department of Pulmonary Disease of the Cocody
University Hospital Center in Abidjan, Côte d'Ivoire from June 2001 to
May 2002. All three patients including 2 women and 1 man were young
Ivorians. Assessment of predisposing factors demonstrated that all three
patients had diminished immune systems resulting from long-term (2-
month) steroid therapy in one patient and AIDS with low rates of CD4 T
cells around 100 cells/microl in 2 patients. Clinical features were
variable but mainly involved constant refractory fever, anaemia,
lymphadenopathy and pleurisy with clear fluid. Despite treatment with
meglumine antimoniate, two patients died within the first weeks.
PMID: 16548498
TITLE: [Early cutaneous leishmaniasis in a 7-day-old newborn]
AUTHORS: K Aoun, A Chetoui, A Rhaiem, J Ghrab, R Dani, A Bouratbine
REFERENCE: Med Trop (Mars) 2005 Sep 65(4):394-5
********************************************************************************************************************
The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
********************************************************************************************************************
PMID: 15345228
TITLE: Leishmania braziliensis isolates differing at the genome level display
distinctive features in BALB/c mice.
AUTHORS: Camila Indiani de Oliveira, Maria Jania Teixeira, Clarissa Romero
Teixeira, JoÃlson Ramos de Jesus, Andréa Bomura Rosato, João Santa da Silva,
Cláudia Brodskyn, Manoel Barral-Netto, Aldina Barral
AFFILIATION: Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Rua
Waldemar Falcão, 121, Salvador, BA 40295-001, Brazil.
REFERENCE: Microbes Infect 2004 Sep 6(11):977-84
Leishmania braziliensis is the species responsible for the majority of
cases of human cutaneous leishmaniasis in Brazil. In the present study,
L. braziliensis isolates from two different geographic areas in Brazil
were studied by RAPD, using arbitrary primers. We also evaluated other
biological features of these two isolates. We compared (a) the clinical
features they initiate or not once delivered subcutaneously as
stationary-phase promastigotes in the footpad of BALB/c mice; (b) the
parasite load in both the footpad and the draining lymph node; (c) the
cytokines present in the supernatant of cultures of the cell suspensions
from the draining lymph nodes; and (d) the cell types present at the
site of parasite delivery. The results show that the L. braziliensis
strain from Ceará (H3227) is genotypically different from the L.
braziliensis strain from Bahia (BA788). H3227-parasitized mice developed
detectable lesions, whereas BA788-parasitized mice did not. Fifteen
days post parasite inoculation there was an increase in the numbers of
macrophages and lymphocytes in the footpads, whatever the parasite
inoculum. Parasite load at the inoculation site--namely the footpad--did
not differ significantly; in draining lymph nodes, however, it
increased over the period under study. Early after parasite inoculation
, the cells recovered from the draining lymph nodes of BA788-parasitized
mice produced higher levels of IFN-gamma, a feature coupled to a higher
number of NK cells. Later, after the parasite inoculation, there was an
increased content of IL-12p70 and IL-10 in the supernatant of cells
recovered from the lymph nodes of H3227-parasitized mice. This
comparative analysis points out that L. braziliensis isolates differing
in their genomic profiles do establish different parasitic processes in
BALB/c mice.
REQUEST: [ leishmania ]
(16 articles match this request. 4 articles matching other requests removed)
PMID: 16388694
TITLE: Approaches for the identification of potential excreted/secreted proteins
of Leishmania major parasites.
AUTHORS: M Chenik, S Lakhal, N Ben Khalef, L Zribi, H Louzir, K Dellagi
AFFILIATION: WHO Collaborating Center for Research and Training in
Leishmaniasis, Laboratoire d'Immunopathologie, Vaccinologie et Génétique
Moléculaire, Institut Pasteur de Tunis, 13, Place Pasteur 1002
Tunis-Belvédére, Tunisia.
REFERENCE: Parasitology 2006 Apr 132(Pt 4):493-509
Leishmania parasites are able to survive in host macrophages despite the
harsh phagolysosomal vacuoles conditions. This could reflect, in part,
their capacity to secrete proteins that may play an essential role in
the establishment of infection and serve as targets for cellular immune
responses. To characterize Leishmania major proteins excreted/secreted
early after promastigote entry into the host macrophage, we have
generated antibodies against culture supernatants of stationary-phase
promastigotes collected 6 h after incubation in conditions that
partially reproduce those prevailing in the parasitophorous vacuole. The
screening of an L. major cDNA library with these antibodies led us to
isolate 33 different cDNA clones that we report here. Sequence analysis
revealed that the corresponding proteins could be classified in 3 groups
: 9 proteins have been previously described as excreted/secreted in
Leishmania and/or other species; 11 correspond to known proteins already
characterized in Leishmania and/or other species although it is unknown
whether they are excreted/secreted and 13 code for unknown proteins.
Interestingly, the latter are transcribed as shown by RT-PCR and some of
them are stage regulated. The L. major excreted/secreted proteins may
constitute putative virulence factors, vaccine candidates and/or new
drug targets.
PMID: 16565502
TITLE: ADP-Ribosylation Factor-Like 3 Is Involved in Kidney and Photoreceptor
Development.
AUTHORS: Jeffrey J Schrick, Peter Vogel, Alejandro Abuin, Billy Hampton, Dennis
S Rice
AFFILIATION: Lexicon Genetics Inc., 8800 Technology Forest Pl., The Woodlands,
TX 77381. jschrick at lexgen.com.
REFERENCE: Am J Pathol 2006 Apr 168(4):1288-98
ADP-ribosylation factor-like 3 (Arl3) is a member of a small subfamily
of G-proteins involved in membrane-associated vesicular and
intracellular trafficking processes. Genetic studies in Leishmania have
shown that the Arl3 homolog is essential for flagellum biogenesis.
Mutations in a related human family member, Arl6, result in Bardet-Biedl
syndrome in humans, which is characterized by genital, renal, and
retinal abnormalities, obesity, and learning deficits. As part of our
large-scale phenotypic screen, mice deficient for the Arl3 gene were
generated and analyzed. Arl3 (-/-) mice were born at a sub-Mendelian
ratio, were small and sickly, and had markedly swollen abdomens. These
mutants failed to thrive, and all died by 3 weeks of age. The (-/-) mice
exhibited abnormal development of renal, hepatic, and pancreatic
epithelial tubule structures, which is characteristic of the renal-
hepatic-pancreatic dysplasia found in autosomal recessive polycystic
kidney disease. Absence of Arl3 was associated with abnormal epithelial
cell proliferation and cyst for-mation. Moreover, mice lacking Arl3
exhibited photoreceptor degeneration as early as postnatal day 14. These
results are the first to implicate Arl3 in a ciliary disease affecting
the kidney, biliary tract, pancreas, and retina.
PMID: 16552085
TITLE: Visceral Leishmania donovani Infection in Interleukin-13-/- Mice.
AUTHORS: Henry W Murray, Christine W Tsai, Jianguo Liu, Xiaojing Ma
AFFILIATION: Department of Medicine, Weill Medical College of Cornell
University, 1300 York Avenue, New York, NY 10021. hwmurray at med.cornell.edu.
REFERENCE: Infect Immun 2006 Apr 74(4):2487-90
Leishmania donovani-infected interleukin-13(-/-) BALB/c mice showed
impaired initial gamma interferon secretion and incomplete granuloma
assembly at parasitized liver foci. Nonetheless, control of early
parasite replication, resolution of liver infection, and responsiveness
to antileishmanial chemotherapy were intact. By itself, interleukin-13
does not appear to materially influence acquired resistance in this
intracellular infection.
PMID: 16416120
TITLE: The putative telomerase reverse transcriptase component of Leishmania
amazonensis: gene cloning and characterization.
AUTHORS: Miriam A Giardini, Cristina B B Lira, Fábio F Conte, Luciana R
Camillo, Jair L de Siqueira Neto, Carlos H I Ramos, Maria Isabel N Cano
AFFILIATION: Departamento de Patologia ClÃnica, Núcleo de Medicina e Cirurgia
Experimental, Faculdade de Ciências Médicas, Universidade Estadual de
Campinas (UNICAMP), CP 6109, Campinas, SP, CEP 13083-970, Brazil.
REFERENCE: Parasitol Res 2006 Apr 98(5):447-54
The Leishmania amazonensis telomerase gene was cloned by a polymerase
chain reaction-based strategy using primers designed from a Leishmania
major sequence that shared similarities with conserved telomerase motifs
. The genes from three other species were cloned for comparative
purposes. A ClustalW multiple-sequence alignment demonstrated that the
Leishmania telomerases show greater homology with each other than with
the proteins of other kinetoplastids and eukaryotes. Characterization
experiments indicated that the putative Leishmania telomerase gene was
probably in single copy and located in the largest chromosomes. A single
messenger ribonucleic acid transcript was found in promastigotes.
Phylogenetic analysis suggested that Leishmania telomerase might
represent a liaison between the oldest and the newest branches of
telomerases.
PMID: 16505138
TITLE: Natural killer cell behavior in lymph nodes revealed by static and
real-time imaging.
AUTHORS: Marc Bajénoff, Béatrice Breart, Alex Y C Huang, Hai Qi, Julie
Cazareth, Veronique M Braud, Ronald N Germain, Nicolas Glaichenhaus
AFFILIATION: Institut National de la Santé et de la Recherche Médicale,
Université de Nice-Sophia Antipolis, E03-44, 06560 Valbonne, France.
REFERENCE: J Exp Med 2006 Mar 203(3):619-31
Natural killer (NK) cells promote dendritic cell (DC) maturation and
influence T cell differentiation in vitro. To better understand the
nature of the putative interactions among these cells in vivo during the
early phases of an adaptive immune response, we have used
immunohistochemical analysis and dynamic intravital imaging to study NK
cell localization and behavior in lymph nodes (LNs) in the steady state
and shortly after infection with Leishmania major. In the LNs of naive
mice, NK cells reside in the medulla and the paracortex, where they
closely associate with DCs. In contrast to T cells, intravital
microscopy revealed that NK cells in the superficial regions of LNs were
slowly motile and maintained their interactions with DCs over extended
times in the presence or absence of immune-activating signals. L. major
induced NK cells to secrete interferon-gamma and to be recruited to the
paracortex, where concomitant CD4 T cell activation occurred. Therefore
, NK cells form a reactive but low mobile network in a strategic area of
the LN where they can receive inflammatory signals, interact with DCs,
and regulate colocalized T cell responses.
PMID: 16533885
TITLE: Infected site-restricted Foxp3+ natural regulatory T cells are specific
for microbial antigens.
AUTHORS: Isabelle J Suffia, Stacie K Reckling, Ciriaco A Piccirillo, Romina S
Goldszmid, Yasmine Belkaid
AFFILIATION: Mucosal Immunology Unit and 2Immunobiology Section, Laboratory of
Parasitic Diseases, National Institute of Allergy and Infectious Diseases
(NIAID), National Institutes of Health (NIH), Bethesda, MD 20892.
REFERENCE: J Exp Med 2006 Mar 203(3):777-88
Natural regulatory T (T reg) cells are involved in control of the immune
response, including response to pathogens. Previous work has
demonstrated that the repertoire of natural T reg cells may be biased
toward self-antigen recognition. Whether they also recognize foreign
antigens and how this recognition contributes to their function remain
unknown. Our studies addressed the antigenic specificity of natural T
reg cells that accumulate at sites of chronic infection with Leishmania
major in mice. Our results support the idea that natural T reg cells are
able to respond specifically to foreign antigens in that they strongly
proliferate in response to Leishmania-infected dendritic cells, they
maintain Foxp3 expression, and Leishmania-specific T reg cell lines can
be generated from infected mice. Surprisingly, the majority of natural T
reg cells at the infected site are Leishmania specific. Further, we
showed that parasite-specific natural T reg cells are restricted to
sites of infection and that their survival is strictly dependent on
parasite persistence.
PMID: 16533268
TITLE: Transfusion medicine illustrated. Electron micrographic study of the
removal of Leishmania from blood products by leukodepletion filters.
AUTHORS: Lisa J Cardo, Ludmila Asher
AFFILIATION: Department of Blood Research, Transfusion Medicine Branch, Walter
Reed Army Institute of Research, Silver Spring, Maryland 20910, USA.
Lisa.Cardo at us.army.mil
REFERENCE: Transfusion 2006 Mar 46(3):315-6
PMID: 16554554
TITLE: A TFIIB-like protein is indispensable for spliced leader RNA gene
transcription in Trypanosoma brucei.
AUTHORS: Bernd Schimanski, Jens Brandenburg, Tu Ngoc Nguyen, Melissa Jo Caimano,
Arthur Günzl
AFFILIATION: Department of Genetics and Developmental Biology, University of
Connecticut Health Center, Farmington, CT 06030, USA.
REFERENCE: Nucleic Acids Res 2006 34(6):1676-84
The lack of general class II transcription factors was a hallmark of the
genomic sequences of the human parasites Trypanosoma brucei,
Trypanosoma cruzi and Leishmania major. However, the recent
identification of TFIIA as part of a protein complex essential for RNA
polymerase II-mediated transcription of SLRNA genes, which encode the
trans splicing-specific spliced leader RNA, suggests that
trypanosomatids assemble a highly divergent set of these factors at the
SLRNA promoter. Here we report the identification of a trypanosomatid
TFIIB-like (TFIIB(like)) protein which has limited overall sequence
homology to eukaryotic TFIIB and archaeal TFB but harbors conserved
residues within the N-terminal zinc ribbon domain, the B finger and
cyclin repeat I. In accordance with the function of TFIIB, T.brucei
TFIIB(like) is encoded by an essential gene, localizes to the nucleus,
specifically binds to the SLRNA promoter, interacts with RNA polymerase
II, and is absolutely required for SLRNA transcription.
PMID: 16539034
TITLE: Selective action of fluoroquinolones against intracellular amastigotes of
Leishmania (Viannia) panamensis in vitro.
AUTHORS: Ibeth C Romero, Nancy G Saravia, John Walker
AFFILIATION: Centro Internacional de Entrenamiento e Investigaciones Médicas,
Cali, Colombia.
REFERENCE: J Parasitol 2005 Dec 91(6):1474-9
We have demonstrated that fluoroquinolones, a class of antibacterial
agents that act through inhibition of type II DNA topoisomerases, exert
selective action against intracellular amastigotes of Leishmania (
Viannia) panamensis at concentrations that are achievable in vivo. Drug
cytotoxicity assays employing the luciferase reporter gene revealed that
intracellular amastigotes were 6.6- to 25.9-fold more sensitive than
human macrophages (P < 0.05) to second-generation fluoroquinolones in
vitro. The most selective agents (enoxacin and ciprofloxacin) exhibited
2 orders of magnitude greater potency against parasites (50% effective
dose [ED50] = 54.9-83.4 microM) than host cells (ED50 = 1,425-1,740
microM). Linear regression analysis of ED50 data confirmed a complete
lack of correlation (r = 0.001) between the relative drug sensitivities
of parasites and host cells. A potential relationship between the
structures of fluoroquinolones and their relative leishmanicidal
activities was observed. The key substituents of the basic pyridone beta
-carboxylic acid nucleus accounting for enhanced antiparasite potency
and selectivity appear to be a nitrogen at position 8 of the bicyclic
nucleus (enoxacin), a cyclopropyl substituent at the R1 site (
ciprofloxacin), and linkage of the R1 and X8 groups by a CH3CHO bridge
to form a tricyclic compound (ofloxacin). These findings support the
potential of fluoroquinolones and derivatives as novel antileishmanials
and encourage their clinical evaluation.
PMID: 16539040
TITLE: Molecular characterization of a human BRCA2 homolog in Leishmania
donovani.
AUTHORS: Smita Misra, Mack Hall, Gautam Chaudhuri
AFFILIATION: Division of Microbial Pathogenesis & Immune Response, Department of
Biomedical Sciences, Meharry Medical College, Nashville, Tennessee 37208, USA.
REFERENCE: J Parasitol 2005 Dec 91(6):1492-5
The breast cancer susceptibility protein BRCA2 is implicated in the DNA
double-strand break (DSB) repair pathway through its association with
Rad51. It is almost a ubiquitous eukaryotic protein; homologs of the
BRCA2 gene (BRH2) have been identified in many mammals, as well as
nonmammals. As a part of our quest to understand the DNA damage, repair
, and recombination process in the parasitic protozoan, Leishmania sp.,
we have cloned and characterized a BRCA2 homolog from Leishmania sp. (
LBRH2). LBRH2 is coded by a single-copy gene (ORF = 3,498 bp) located at
the 700-kb chromosome 16. The transcripts in both the promastigotes and
the amastigotes are approximately 3.9 kilonucleotides (knt) in size,
corresponding to a protein with a calculated molecular mass of 128 kDa.
The primary transcript of the gene is alternatively trans-spliced to
produce 3 distinct mRNAs with altered folded structures at their 5' ends
. This study will contribute toward the understanding of a potential
RAD51-mediated DNA recombination/repair pathway in Leishmania sp.
PMID: 16539044
TITLE: Molecular characterization of the hexokinase gene from Leishmania major.
AUTHORS: Perunthottathu K Umasankar, P Cyril Jayakumar, Yogesh S Shouche,
Millind S Patole
AFFILIATION: National Centre for Cell Science, University of Pune Campus, Ganesh
Khind, India.
REFERENCE: J Parasitol 2005 Dec 91(6):1504-9
The coding sequence for hexokinase enzyme was cloned from Leishmania
major. The sequence was found to encode an enzyme with a molecular mass
of 51.74 kDa. Amino acid sequence showed maximum homology with known
trypanosome and plant hexokinases. It has a calculated isoelectric point
of 8.46 and contains an N-terminal peroxisome-targeting signal, the
characteristics frequently associated with glycosomal proteins. The
sequence indicated the presence of conserved amino acid residues and
motifs that are present in plant and mammalian hexokinases; these are
apparently involved in the binding of different substrates. The L. major
genome was found to have 2 copies of hexokinase coding sequences in
tandem with an intergenic spacer of 2.58 kb. Both the genes in the
hexokinase locus were transcribed as individual transcripts in a
monocistronic form, having the same size as seen by Northern blot
analysis. The hexokinase gene was transcribed in large amounts in the
promastigote stage, whereas there is only weak expression in the
amastigote stage as determined by RT-PCR analysis. Sequencing of
hexokinase loci from different Leishmania species (e.g., L. donovani, L
. infantum, L. tropica, and L. mexicana) revealed that the hexokinase
locus is highly conserved at the DNA and protein levels among species of
Leishmania compared with trypanosomes.
********************************************************************************************************************
The following references are revised files and are brought to you in accordance
to license agreement with the NLM.
********************************************************************************************************************
PMID: 15777918
TITLE: Ploidy changes associated with disruption of two adjacent genes on
Leishmania major chromosome 1.
AUTHORS: Santiago MartÃnez-Calvillo, Kenneth Stuart, Peter J Myler
AFFILIATION: Seattle Biomedical Research Institute, 307 Westlake Ave. N.,
Seattle, WA 98109-5219, USA.
REFERENCE: Int J Parasitol 2005 Apr 35(4):419-29
Leishmania major Friedlin (LmjF) is a kinetoplastid protozoan whose
genomic sequence has been recently elucidated. About 60% of the
identified genes do not have a known function, and many are
trypanosomatid-specific. Here we characterise two adjacent genes from
LmjF chromosome 1 (chr1): LmjF01.0750, which encodes a predicted protein
with a serine/threonine protein kinase motif and LmjF01.0760, which
encodes a product with no similarity to other known proteins.
Orthologues of both genes are present in Trypanosoma cruzi, but neither
occur in Trypanosoma brucei. We have mapped polyadenylation and spliced-
leader acceptor sites for both genes, and show that they differ between
Leishmania species. Attempts to generate null mutants of LmjF01.0750 by
homologous recombination were unsuccessful and led to the apparent
triploidy of the entire genome, suggesting that it is an essential gene
. Interestingly, at least two copies of LmjF01.0750 are required for
cell survival. Further evidence of genome plasticity in Leishmania was
provided by changes in chr1 copy number that occurred during in vitro
growth of wild-type LmjF promastigotes and following replacement of a
single copy of LmjF01.0760.
REQUEST: [ sand fly ]
(0 articles match this request)
REQUEST: [ sandfly ]
(0 articles match this request)
You receive this email because you requested RefScout®'s literature
update.
If you would like to change or add requests, please go to your user
profile.
If you can't read our newsletter, please resend newsletter back to us to
info at refscout.com, including information
about your operating system and mail client software you use, and we will do
our
best to solve the problem.
If you would like to be removed from RefScout®'s literature service, please
press the
remove button.
DISCLAIMER
----- End forwarded message -----
More information about the Leish-l
mailing list